rs1074182

Variant names:

• chr16-53437445-T-G
• rs1074182
• NM_005611.4:c.241-1571T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005611.4(RBL2):​c.241-1571T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 151,938 control chromosomes in the GnomAD database, including 24,189 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (24189 hom., cov: 31)
• Consequence: RBL2 NM_005611.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.572
• Publications: 11 publications found

Genes affected

RBL2 (HGNC:9894): (RB transcriptional corepressor like 2) Enables promoter-specific chromatin binding activity. Involved in regulation of lipid kinase activity. Acts upstream of or within negative regulation of gene expression. Located in chromosome; cytosol; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

RBL2 Gene-Disease associations (from GenCC):

• Brunet-Wagner neurodevelopmental syndrome

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBL2	NM_005611.4	c.241-1571T>G		intron_variant	Intron 1 of 21	ENST00000262133.11	NP_005602.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBL2	ENST00000262133.11	c.241-1571T>G		intron_variant	Intron 1 of 21	1	NM_005611.4	ENSP00000262133.6
RBL2	ENST00000544405.6	c.19-1571T>G		intron_variant	Intron 1 of 14	2		ENSP00000443744.2
RBL2	ENST00000567964.6	c.-153-1571T>G		intron_variant	Intron 1 of 5	5		ENSP00000462464.1
RBL2	ENST00000680543.1	n.380-1571T>G		intron_variant	Intron 1 of 20

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81645 AN: 151820 Hom.: 24144 Cov.: 31

Gnomad AFR AF: 0.782

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.546

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.538 AC: 81743 AN: 151938 Hom.: 24189 Cov.: 31 AF XY: 0.528 AC XY: 39209 AN XY: 74238

African (AFR) AF: 0.783 AC: 32448 AN: 41460

American (AMR) AF: 0.445 AC: 6786 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 2055 AN: 3468

East Asian (EAS) AF: 0.181 AC: 934 AN: 5162

South Asian (SAS) AF: 0.472 AC: 2274 AN: 4822

European-Finnish (FIN) AF: 0.349 AC: 3679 AN: 10532

Middle Eastern (MID) AF: 0.661 AC: 193 AN: 292

European-Non Finnish (NFE) AF: 0.469 AC: 31835 AN: 67924

Other (OTH) AF: 0.551 AC: 1159 AN: 2104

Alfa AF: 0.510 Hom.: 3322

Bravo AF: 0.550

Asia WGS AF: 0.422 AC: 1471 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.15
DANN	Benign	0.48
PhyloP100		-0.57
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1074182; hg19: chr16-53471357;